MAOI

Monoamine oxidase inhibitors (also known as MAOIs) are a class of drugs which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression and are particularly effective in treating atypical depression.[1] They are also used in the treatment of Parkinson's disease and several other disorders.[citation needed]

Mechanism of action

MAOIs act by inhibiting the activity of monoamine oxidase, preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B.

Reversibility

The early MAOIs inhibit monoamine oxidase irreversibly, meaning they permanently deactivate it and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. A few newer MAOIs, known as reversible inhibitors of monoamine oxidase A (RIMAs), are reversible. This means that they are able to detach from the enzyme to facilitate usual catabolism of the substrate.[citation needed]

Substances that inhibits the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times.
When the CYP450 system is impacted in this way, it leads to higher levels of certain drugs in your system at one time. This can cause unwanted side effects, and sometimes, an overdose.

This section will never be complete since too many substances interact with MAOIs. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption. However, not everything is documented and animal studies is not always reliable, so always start with microdoses.

Tyramine

Tyramine causes hypertensive crises after MAO inhibition aka the "cheese effect" or "cheese crisis". Using a MAO inhibitor (MAOI), the intake of approximately 10 to 25 mg of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild reaction.[3] Tyramine rich food should also be avoided by people prone to headache and migraine.

Psychoactive substances

Naturally occurring sources with tyramine.

Psychedelic cacti. The cacti contain contain a bunch of phenethylamines, not just tyramine (but also 3-Methoxytyramine, methyltyramine, hordenine (aka dimethyltyramine), mescaline, etc) and should thus be avoided with MAOIs. However, tyramine has been identified in these species:

Tyramine formation has been associated with bacterial contamination of foods or temperature abuse conditions, but can also occur as a side effect of generally desired ripening processes.[8] Tyramine is a breakdown product of the amino acid L-tyrosine.

Psychoactive substances

The MAOIs are well-known for their numerous drug interactions, including the following kinds of substances:

Substances that are metabolized by monoamine oxidase, as they can be boosted by up to several-fold

Substances that increase serotonin, noradrenaline, or dopamine activity as too much of any of these neurotransmitters can result in severe acute consequences including serotonin syndrome, hypertensive crisis, and psychosis.

Long-term use with psychoactive substances that interact with MAOIs must be gradually discontinued to avoid discontinuation syndrome. Examples:

Cannabinoids: Cannabinoids are lipophilic. For example, THC has been detected in heavy cannabis users after 77 days of drug abstinence (Ellis et al., 1985).[12]

SSRIs: Because of the extended half-life of norfluoxetine, a minimum of 5 weeks should lapse between stopping fluoxetine (20 mg/day) and starting an MAOI. With higher doses the interval should be longer. For example, a serotonin syndrome was reported following a 6-weeks washout in a patient who had been given fluoxetine (80 mg/day).[13]

Opioids: Some opioid analgesics are associated with a risk of serotonin syndrome in combination with MAOIs due to their serotonergic properties. Other combinations may result in opioid toxicity due to CYP450 enzyme inhibition by the MAOI. Given the widespread availability of several suitable alternative drugs, the combination of dextromethorphan, methadone, pethidine, tramadol, fentanyl or tapentadol with an MAOI should usually be avoided, including in the 14 day period following the withdrawal of an irreversible MAOI. Morphine, codeine, oxycodone and buprenorphine are alternative opioids for patients receiving MAOIs, though starting at a low dose and titrating cautiously against clinical response is advised.[18]